Objective: This study investigated the expression of P-type copper transporting adenosine triphosphatase ATP7A in the tumor tissues of patients with advanced esophageal squamous cell carcinoma (ESCC), and analyzed its correlation to clinicopathologic features and prognosis of advanced ESCC patients. Methods: The expression of ATP7A protein in 49 specimens of advanced ESCC patients who were treated with first line cisplatin-based chemotherapy without surgery or radiotherapy, was detected by immunohistochemistry. The correlation of ATP7A expression with clinicopathologic features and prognosis of advanced ESCC patients weas analyzed by SPSS 16.0 statistical software package. Results: Positive ATP7A staining was observed in cytoplasm of ESCC cells in 44. of tumors (22 of 49 cases), but was not detected in adjacent stroma of tumor tissue. ATP7A expression status was correlated with response to histologic grade and cisplatin-based chemotherapy (P values 0.02, 0.028 respectively). No significant association was found between ATP7A expression and age (P=0.085), gender (P=0.74), or PS (P=0.56). Kaplan-Meier analysis indicated that advanced ESCC patients positive for ATP7A positive had overall survival (OS) inferior to advanced ESCC patients who were ATP7A negative (P value was 0.037 by log-rank test). In univariate analysis, histologic grade and ATP7A expression were significantly correlated with OS (P=0.011 and 0.049 respectively); in multivariate analysis, histologic grade and ATP7A were independent factors significantly related to OS for advanced ESCC patients treated by cisplatin-based chemotherapy (P values 0.039 and 0.043 respectively). Conclusion: ATP7A was positively expressed in the majority of advanced ESCC tissues. The expression level of ATP7A was an important factor affecting tumor tissue's histologic grade, the response to platinum-based chemotherapy and the prognosis of advanced ESCC patients. This indicates that ATP7A might be involved in the genesis and development of ESCC, and could be a resistance marker for platinum-based chemotherapy, and a prognostic factor for survival in patients with ESCC treated by Pt-based chemotherapy.